The Annual Review of Pharmacology and Toxicology,
Journal Year:
2020,
Volume and Issue:
61(1), P. 779 - 803
Published: Sept. 30, 2020
Senescence
is
the
consequence
of
a
signaling
mechanism
activated
in
stressed
cells
to
prevent
proliferation
with
damage.
Senescent
(Sncs)
often
develop
senescence-associated
secretory
phenotype
prompt
immune
clearance,
which
drives
chronic
sterile
inflammation
and
plays
causal
role
aging
age-related
diseases.
Sncs
accumulate
age
at
anatomical
sites
disease.
Thus,
they
are
regarded
as
logical
therapeutic
target.
Senotherapeutics
new
class
drugs
that
selectively
kill
(senolytics)
or
suppress
their
disease-causing
phenotypes
(senomorphics/senostatics).
Since
2015,
several
senolytics
went
from
identification
clinical
trial.
Preclinical
data
indicate
alleviate
disease
numerous
organs,
improve
physical
function
resilience,
all
causes
mortality,
even
if
administered
aged.
Here,
we
review
evidence
drive
disease,
approaches
identify
optimize
senotherapeutics,
current
status
preclinical
testing
senolytics.
Open Biology,
Journal Year:
2020,
Volume and Issue:
10(9)
Published: Sept. 1, 2020
Wound
healing
is
a
complex,
dynamic
process
supported
by
myriad
of
cellular
events
that
must
be
tightly
coordinated
to
efficiently
repair
damaged
tissue.
Derangement
in
wound-linked
behaviours,
as
occurs
with
diabetes
and
ageing,
can
lead
impairment
the
formation
chronic,
non-healing
wounds.
These
wounds
are
significant
socioeconomic
burden
due
their
high
prevalence
recurrence.
Thus,
there
an
urgent
requirement
for
improved
biological
clinical
understanding
mechanisms
underpin
wound
repair.
Here,
we
review
basis
tissue
discuss
how
current
emerging
pathology
could
inform
future
development
efficacious
therapies.
Genes & Development,
Journal Year:
2020,
Volume and Issue:
34(23-24), P. 1565 - 1576
Published: Dec. 1, 2020
Cellular
senescence
is
a
stress
response
that
elicits
permanent
cell
cycle
arrest
and
triggers
profound
phenotypic
changes
such
as
the
production
of
bioactive
secretome,
referred
to
senescence-associated
secretory
phenotype
(SASP).
Acute
induction
protects
against
cancer
limits
fibrosis,
but
lingering
senescent
cells
drive
age-related
disorders.
Thus,
targeting
delay
aging
limit
dysfunction,
known
“senotherapy,”
gaining
momentum.
While
drugs
selectively
kill
cells,
termed
“senolytics”
are
major
focus,
SASP-centered
approaches
emerging
alternatives
target
diseases.
Here,
we
summarize
regulation
functions
SASP
highlight
therapeutic
potential
modulation
complimentary
or
an
alternative
current
senolytic
approaches.
Journal of Internal Medicine,
Journal Year:
2020,
Volume and Issue:
288(5), P. 518 - 536
Published: July 20, 2020
Senolytics
are
a
class
of
drugs
that
selectively
clear
senescent
cells
(SC).
The
first
senolytic
Dasatinib,
Quercetin,
Fisetin
and
Navitoclax
were
discovered
using
hypothesis-driven
approach.
SC
accumulate
with
ageing
at
causal
sites
multiple
chronic
disorders,
including
diseases
accounting
for
the
bulk
morbidity,
mortality
health
expenditures.
most
deleterious
resistant
to
apoptosis
have
up-regulation
anti-apoptotic
pathways
which
defend
against
their
own
inflammatory
senescence-associated
secretory
phenotype
(SASP),
allowing
them
survive,
despite
killing
neighbouring
cells.
transiently
disable
these
SCAPs,
causing
those
tissue-destructive
SASP.
Because
take
weeks
reaccumulate,
senolytics
can
be
administered
intermittently
-
'hit-and-run'
In
preclinical
models,
delay,
prevent
or
alleviate
frailty,
cancers
cardiovascular,
neuropsychiatric,
liver,
kidney,
musculoskeletal,
lung,
eye,
haematological,
metabolic
skin
disorders
as
well
complications
organ
transplantation,
radiation
cancer
treatment.
As
anticipated
agents
targeting
fundamental
mechanisms
'root
cause'
contributors
potential
uses
protean,
potentially
alleviating
over
40
conditions
in
studies,
opening
new
route
treating
age-related
dysfunction
diseases.
Early
pilot
trials
suggest
they
decrease
cells,
reduce
inflammation
frailty
humans.
Clinical
diabetes,
idiopathic
pulmonary
fibrosis,
Alzheimer's
disease,
COVID-19,
osteoarthritis,
osteoporosis,
eye
bone
marrow
transplant
childhood
survivors
underway
beginning.
Until
such
studies
done,
it
is
too
early
used
outside
clinical
trials.
Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: May 22, 2023
Abstract
Macrophages
exist
in
various
tissues,
several
body
cavities,
and
around
mucosal
surfaces
are
a
vital
part
of
the
innate
immune
system
for
host
defense
against
many
pathogens
cancers.
possess
binary
M1/M2
macrophage
polarization
settings,
which
perform
central
role
an
array
tasks
via
intrinsic
signal
cascades
and,
therefore,
must
be
precisely
regulated.
Many
crucial
questions
about
signaling
modulation
yet
to
uncovered.
In
addition,
clinical
importance
tumor-associated
macrophages
is
becoming
more
widely
recognized
as
significant
progress
has
been
made
understanding
their
biology.
Moreover,
they
integral
tumor
microenvironment,
playing
regulation
wide
variety
processes
including
angiogenesis,
extracellular
matrix
transformation,
cancer
cell
proliferation,
metastasis,
immunosuppression,
resistance
chemotherapeutic
checkpoint
blockade
immunotherapies.
Herein,
we
discuss
signaling,
mechanical
stresses
modulation,
metabolic
pathways,
mitochondrial
transcriptional,
epigenetic
regulation.
Furthermore,
have
broadly
extended
traps
essential
roles
autophagy
aging
regulating
functions.
discussed
recent
advances
macrophages-mediated
autoimmune
diseases
tumorigenesis.
Lastly,
targeted
therapy
portray
prospective
targets
therapeutic
strategies
health
diseases.
Signal Transduction and Targeted Therapy,
Journal Year:
2022,
Volume and Issue:
7(1)
Published: Dec. 16, 2022
Aging
is
a
gradual
and
irreversible
pathophysiological
process.
It
presents
with
declines
in
tissue
cell
functions
significant
increases
the
risks
of
various
aging-related
diseases,
including
neurodegenerative
cardiovascular
metabolic
musculoskeletal
immune
system
diseases.
Although
development
modern
medicine
has
promoted
human
health
greatly
extended
life
expectancy,
aging
society,
variety
chronic
diseases
have
gradually
become
most
important
causes
disability
death
elderly
individuals.
Current
research
on
focuses
elucidating
how
endogenous
exogenous
stresses
(such
as
genomic
instability,
telomere
dysfunction,
epigenetic
alterations,
loss
proteostasis,
compromise
autophagy,
mitochondrial
cellular
senescence,
stem
exhaustion,
altered
intercellular
communication,
deregulated
nutrient
sensing)
participate
regulation
aging.
Furthermore,
thorough
pathogenesis
to
identify
interventions
that
promote
longevity
caloric
restriction,
microbiota
transplantation,
nutritional
intervention)
clinical
treatment
methods
for
(depletion
senescent
cells,
therapy,
antioxidative
anti-inflammatory
treatments,
hormone
replacement
therapy)
could
decrease
incidence
turn
healthy
longevity.
Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: June 8, 2023
Abstract
Aging
is
characterized
by
systemic
chronic
inflammation,
which
accompanied
cellular
senescence,
immunosenescence,
organ
dysfunction,
and
age-related
diseases.
Given
the
multidimensional
complexity
of
aging,
there
an
urgent
need
for
a
systematic
organization
inflammaging
through
dimensionality
reduction.
Factors
secreted
senescent
cells,
known
as
senescence-associated
secretory
phenotype
(SASP),
promote
inflammation
can
induce
senescence
in
normal
cells.
At
same
time,
accelerates
immune
resulting
weakened
function
inability
to
clear
cells
inflammatory
factors,
creates
vicious
cycle
senescence.
Persistently
elevated
levels
organs
such
bone
marrow,
liver,
lungs
cannot
be
eliminated
leading
damage
aging-related
Therefore,
has
been
recognized
endogenous
factor
elimination
could
potential
strategy
anti-aging.
Here
we
discuss
at
molecular,
cellular,
organ,
disease
levels,
review
current
aging
models,
implications
cutting-edge
single
cell
technologies,
well
anti-aging
strategies.
Since
preventing
alleviating
diseases
improving
overall
quality
life
are
ultimate
goals
research,
our
highlights
critical
features
mechanisms
along
with
latest
developments
future
directions
providing
theoretical
foundation
novel
practical
